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Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter

Oncogene volume 26, pages 633–640 (2007)Cite this article

Abstract

Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription–PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

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Author notes

  1. B Joshi

    Present address: Department of Cellular and Physiological Sciences, University of British Columbia, 2177 Wesbrook Mall, Vancouver, British Columbia, Canada, V6T 1Z3

  2. F L Delarue and J Adnane: These authors contributed equally to this work.

Authors and Affiliations

  1. Drug Discovery Program at H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    F L Delarue, J Adnane, B Joshi, M A Blaskovich, D-A Wang, J Hawker, F Bizouarn, K Zhu, S Chellappan & S M Sebti

  2. Departments of Oncology and Biochemistry and Molecular Biology, University of South Florida, Tampa, FL, USA

    F L Delarue, J Adnane, B Joshi, D-A Wang, J Hawker, F Bizouarn, K Zhu, S Chellappan & S M Sebti

  3. Department of Chemistry, Yale University, New Haven, CT, USA

    J Ohkanda & A D Hamilton

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  1. F L Delarue
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Correspondence to S M Sebti.

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Delarue, F., Adnane, J., Joshi, B. et al. Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Oncogene 26, 633–640 (2007). https://doi.org/10.1038/sj.onc.1209819

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  • DOI: https://doi.org/10.1038/sj.onc.1209819

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